Aesthetic Reconstruction of the Sequelae of Large Facial Involuted Infantile Hemangioma with Tissue Expanders.

BACKGROUND: Large involuted infantile hemangioma remains a challenge in facial reconstruction. The characteristic fibrofatty residuum and multiple subunits/tissues involvement contribute significantly to the difficulty of surgical management. Tissue expander plays an important role in facial reconstruction, allowing plastic surgeons to repair skin damaged by both congenital and acquired defects. METHODS: Between 2009 and 2021, 30 patients who underwent tissue expansion surgery were reviewed in a single hospital. The demographic data, lesion characteristics, surgical approaches, complication rate, and aesthetic outcomes were analyzed. RESULTS: Thirty patients (5 men and 25 women) with a mean age of 14.03 ± 7.25 years (range, 4-33 years) were included. The mean follow-up is 35.92 months, ranging from 9 to 75 months. Tissue expansion-related complications include closed infection, 2/30 (6.67%); skin ischemia, 2/30 (6.67%); hematoma, 1/30 (3.33%); flap necrosis, 1/30 (3.33%). CONCLUSION: Large facial involuted infantile hemangiomas have variable patterns of presentation and necessitate tailored therapy. Tissue expansion is a reproducible approach to achieving aesthetic reconstruction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Ku70 Binding to YAP Alters PARP1 Ubiquitination to Regulate Genome Stability and Tumorigenesis.

YAP is a central player in cancer development with functions extending beyond its recognized role in cell growth regulation. Recent work has identified a link between YAP/TAZ and the DNA damage response. Here, we investigated the mechanistic underpinnings of the crosstalk between DNA damage repair and YAP activity. Ku70, a key component of the non-homologous end joining pathway to repair DNA damage, engaged in a dynamic competition with TEAD4 for binding to YAP, limiting the transcriptional activity of YAP. Depletion of Ku70 enhanced interaction between YAP and TEAD4 and boosted YAP transcriptional capacity. Consequently, Ku70 loss enhanced tumorigenesis in colon cancer and hepatocellular carcinoma (HCC) in vivo. YAP impeded DNA damage repair and elevated genome instability by inducing PARP1 degradation through the SMURF2-mediated ubiquitin-proteasome pathway. Analysis of HCC patient samples substantiated the link between Ku70 expression, YAP activity, PARP1 levels, and genome instability. In conclusion, this research provides insight into the mechanistic interactions between YAP and key regulators of DNA damage repair, highlighting the role of a Ku70-YAP-PARP1 axis in preserving genome stability.

Rhizophagus irregularis and biochar can synergistically improve the physiological characteristics of saline-alkali resistance of switchgrass.

Inoculation of arbuscular mycorrhizal fungi (AMF) or biochar (BC) application can improve photosynthesis and promote plant growth under saline-alkali stress. However, little is known about the effects of the two combined on growth and physiological characteristics of switchgrass under saline-alkali stress. This study examined the effects of four treatments: (1) no AMF inoculation and no biochar addition (control), (2) biochar (BC) alone, (3) AMF (Rhizophagus irregularis, Ri) alone, and (4) the combination of both (BC+Ri) on the plant biomass, antioxidant enzymes, chlorophyll, and photosynthetic parameters of switchgrass under saline-alkali stress. The results showed that the above-ground, belowground and total biomass of switchgrass in the BC+Ri treatment group was significantly higher (+136.7%, 120.2% and 132.4%, respectively) than in other treatments compared with Control. BC+Ri treatment significantly increased plant leaves' relative chlorophyll content, antioxidant enzyme activity, and photosynthesis parameters. It is worth noting that the transpiration rate, stomatal conductance, net photosynthetic rate, PSII efficiency and other photosynthetic-related indexes of the BC+Ri treatment group were the highest (38% to 54% higher than other treatments). The fitting results of light response and CO2 response curves showed that the light saturation point, light compensation point, maximum carboxylation rate and maximum electron transfer rate of switchgrass in the Ri+BC treatment group were the highest. In conclusion, biochar combined with Ri has potential beneficial effects on promoting switchgrass growth under saline-alkali stress and improving the activity of antioxidant enzymes and photosynthetic characteristics of plants.

Reorganization of motor network in patients with Parkinson's disease after deep brain stimulation.

AIMS: Parkinson's disease (PD) patients experience improvement in motor symptoms after deep brain stimulation (DBS) and before initiating stimulation. This is called the microlesion effect. However, the mechanism remains unclear. The study aims to comprehensively explore the changes in functional connectivity (FC) patterns in movement-related brain regions in PD patients during the microlesion phase through seed-based FC analysis. METHODS: The study collected the resting functional magnetic resonance imaging data of 49 PD patients before and after DBS surgery (off stimulation). The cortical and subcortical areas related to motor function were selected for seed-based FC analysis. Meanwhile, their relationship with the motor scale was investigated. RESULTS: The motor-related brain regions were selected as the seed point, and we observed various FC declines within the motor network brain regions. These declines were primarily in the left middle temporal gyrus, bilateral middle frontal gyrus, right supplementary motor area, left precentral gyrus, left postcentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus after DBS. CONCLUSION: The movement-related network was extensively reorganized during the microlesion period. The study provided new information on enhancing motor function from the network level post-DBS.

Practical surgical technique using the SMISS approach for lip reduction in involuted lip infantile hemangiomas.

BACKGROUND: Lip infantile hemangiomas tend to show less volumetric regression and are more susceptible to visible sequelae in the involuted stage. Some of them still require surgical management after propranolol therapy. This study aimed to evaluate the efficacy and safety of the Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach applied to lip reduction for those with involuted lip hemangiomas. METHODS: A retrospective review was performed to evaluate patients with lip hemangioma who received previous propranolol treatment and underwent the aforementioned procedure. Demographic characteristics, lesion morphology, and medical history were reviewed. The Visual Analog Scale was applied to assess the postoperative appearance. Complications within 12 months postoperatively were recorded. RESULTS: A total of 18 patients with lip hemangioma were eligible. All patients received oral propranolol therapy before surgery, with treatment duration ranging from 6.0 to 23.0 months. Their age at surgery ranged from 2.5 to 9.0 years. The median Visual Analog Scale scores were 8.0, ranging from 4.0 to 10.0. No severe complications were reported. CONCLUSIONS: This modified technique based on the SMISS approach has proven reliable and effective in improving the aesthetic outcome for involuted lip infantile hemangiomas. Practical surgical techniques still play an important part in the propranolol era.

Systematic evaluation of single-cell RNA-seq analyses performance based on long-read sequencing platforms.

INTRODUCTION: The rapid development of next-generation sequencing (NGS)-based single-cell RNA sequencing (scRNA-seq) allows for detecting and quantifying gene expression in a high-throughput manner, providing a powerful tool for comprehensively understanding cellular function in various biological processes. However, the NGS-based scRNA-seq only quantifies gene expression and cannot reveal the exact transcript structures (isoforms) of each gene due to the limited read length. On the other hand, the long read length of third-generation sequencing (TGS) technologies, including Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio), enable direct reading of intact cDNA molecules. OBJECTIVES: Both ONT and PacBio have been used in conjunction with scRNA-seq, but their performance in single-cell analyses has not been systematically evaluated. METHODS: To address this, we generated ONT and PacBio data from the same single-cell cDNA libraries containing different amount of cells. RESULTS: Using NGS as a control, we assessed the performance of each platform in cell type identification. Additionally, the reliability in identifying novel isoforms and allele-specific gene/isoform expression by both platforms was verified, providing a systematic evaluation to design the sequencing strategies in single-cell transcriptome studies. CONCLUSION: Beyond gene expression analysis, which the NGS-based scRNA-seq only affords, TGS-based scRNA-seq achieved gene splicing analyses, identifying novel isoforms. Attribute to higher sequencing quality of PacBio, it outperforms ONT in accuracy of novel transcripts identification and allele-specific gene/isoform expression.

Droplet Hi-C for Fast and Scalable Profiling of Chromatin Architecture in Single Cells.

Comprehensive analysis of chromatin architecture is crucial for understanding the gene regulatory programs during development and in disease pathogenesis, yet current methods often inadequately address the unique challenges presented by analysis of heterogeneous tissue samples. Here, we introduce Droplet Hi-C, which employs a commercial microfluidic device for high-throughput, single-cell chromatin conformation profiling in droplets. Using Droplet Hi-C, we mapped the chromatin architecture at single-cell resolution from the mouse cortex and analyzed gene regulatory programs in major cortical cell types. Additionally, we used this technique to detect copy number variation (CNV), structural variations (SVs) and extrachromosomal DNA (ecDNA) in cancer cells, revealing clonal dynamics and other oncogenic events during treatment. We further refined this technique to allow for joint profiling of chromatin architecture and transcriptome in single cells, facilitating a more comprehensive exploration of the links between chromatin architecture and gene expression in both normal tissues and tumors. Thus, Droplet Hi-C not only addresses critical gaps in chromatin analysis of heterogeneous tissues but also emerges as a versatile tool enhancing our understanding of gene regulation in health and disease.

Hippocampal excitation-inhibition balance underlies the 5-HT2C receptor in modulating depressive behaviours.

The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in depression is a topic of debate, and the underlying mechanisms remain largely unclear. We now elucidate hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed that inhibition of 5-HT2CR induced depressive-like behaviors, reduced GABA release and shifted the E/I balance towards excitation in CA3 pyramidal neurons by using behavioral analyses, microdialysis coupled with mass spectrum, and electrophysiological recording. Moreover, 5-HT2CR modulated neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction through influencing intracellular Ca2+ release, as determined by fiber photometry and coimmunoprecipitation. Notably, disruption of nNOS-CAPON by specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP, abolished 5-HT2CR inhibition-induced depressive-like behaviors, as well as the impairment in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly-mediated GABA vesicle release and a consequent E/I imbalance. Importantly, optogenetic inhibition of CA3 GABAergic neurons prevented the effects of AAV-CMV-CAPON-125C-GFP on depressive behaviors in the presence of 5-HT2CR antagonist. Conclusively, our findings disclose the regulatory role of 5-HT2CR in depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

Effects of Lactobacillus plantarum fermentation on the structure, physicochemical properties, and digestibility of foxtail millet starches.

This study investigated the effects of Lactobacillus plantarum fermentation on the structural, physicochemical, and digestive properties of foxtail millet starches. The fermented starch granules formed a structure with honeycomb-like dents, uneven pores, and reduced particle size. As the fermentation time extended, the amylose content of waxy (0.88 %) and non-waxy (33.71 %) foxtail millet starches decreased to the minimum value at 24 h (0.59 % and 29.19 %, respectively), and then increased to 0.85 % and 31.87 % at 72 h, respectively. Both native and fermented foxtail millet starches exhibited an A-type crystal structure. Compared with native samples, the fermented samples performed enhanced proportion of short-branched chain, crystallinity, and short-range ordered degree. After fermentation for 24 h, the solubility, adsorption capacity, and pasting viscosity of foxtail millet starches improved, whereas the swelling power, pasting temperature, breakdown, setback, and degree of retrogradation reduced. Additionally, fermentation increased the transition temperatures, enthalpy, and digestibility. Overall, Lactobacillus plantarum fermentation is considered a competent choice to regulate the characteristics of foxtail millet starch.

The impacts of early environmental adversity on cognitive functioning, body mass, and life-history behavioral profiles.

Early adverse experiences or exposures have a profound impact on neurophysiological, cognitive, and somatic development. Evidence across disciplines uncovers adversity-induced alternations in cortical structures, cognitive functions, and related behavioral manifestations, as well as an energetic trade-off between the brain and body. Based on the life history (LH) framework, the present research aims to explore the adversity-adapted cognitive-behavioral mechanism and investigate the relation between cognitive functioning and somatic energy reserve (i.e., body mass index; BMI). A structural equation modeling (SEM) analysis was performed with longitudinal self-reported, anthropometric, and task-based data drawn from a cohort of 2,607 8- to 11-year-old youths and their primary caregivers recruited by the Adolescent Brain Cognitive Development (ABCDSM) study. The results showed that early environmental adversity was positively associated with fast LH behavioral profiles and negatively with cognitive functioning. Moreover, cognitive functioning mediated the relationship between adversity and fast LH behavioral profiles. Additionally, we found that early environmental adversity positively predicted BMI, which was inversely correlated with cognitive functioning. These results revealed an adversity-adapted cognitive-behavioral mechanism and energy-allocation pathways, and add to the existing knowledge of LH trade-off and developmental plasticity.

Individualism, collectivism and conformity in nine countries: Relations with parenting and child adjustment.

This study investigated how individualism, collectivism and conformity are associated with parenting and child adjustment in 1297 families with 10-year-old children from 13 cultural groups in nine countries. With multilevel models disaggregating between- and within-culture effects, we examined between- and within-culture associations between maternal and paternal cultural values, parenting dimensions and children's adjustment. Mothers from cultures endorsing higher collectivism and fathers from cultures endorsing lower individualism engage more frequently in warm parenting behaviours. Mothers and fathers with higher-than-average collectivism in their culture reported higher parent warmth and expectations for children's family obligations. Mothers with higher-than-average collectivism in their cultures more frequently reported warm parenting and fewer externalising problems in children, whereas mothers with higher-than-average individualism in their culture reported more child adjustment problems. Mothers with higher-than-average conformity values in their culture reported more father-displays of warmth and greater mother-reported expectations for children's family obligations. Fathers with higher-than-average individualism in their culture reported setting more rules and soliciting more knowledge about their children's whereabouts. Fathers who endorsed higher-than-average conformity in their culture displayed more warmth and expectations for children's family obligations and granted them more autonomy. Being connected to an interdependent, cohesive group appears to relate to parenting and children's adjustment.

The severity assessment of Parkinson's disease based on plasma inflammatory factors and third ventricle width by transcranial sonography.

BACKGROUND: Predicting Parkinson's disease (PD) can provide patients with targeted therapies. However, disease severity can be roughly evaluated in clinical practice based on the patient's symptoms and signs. OBJECTIVE: The current study attempted to explore the factors linked with PD severity and construct a predictive model. METHOD: The PD patients and healthy controls were recruited from our study center while recording their basic demographic information. The serum inflammatory markers levels, such as Cystatin C (Cys C), C-reactive protein (CRP), RANTES (regulated on activation, normal T cell expressed and secreted), Interleukin-10 (IL-10), and Interleukin-6 (IL-6) were determined for all the participants. PD patients were categorized into early and mid-advanced groups based on the Hoehn and Yahr (H-Y) scale and evaluated using PD-related scales. LASSO logistic regression analysis (Model C) helped select variables based on clinical scale evaluations, serum inflammatory factor levels, and transcranial sonography measurements. The optimal harmonious model coefficient λ was determined via 10-fold cross-validation. Moreover, Model C was compared with multivariate (Model A) and stepwise (Model B) logistic regression. The area under the curve (AUC) of a receiver operator characteristic (ROC), brier score, calibration curve, and decision curve analysis (DCA) helped determine the discrimination and calibration of the predictive model, followed by configuring a forest plot and column chart. RESULTS: The study included 113 healthy individuals and 102 PD patients, with 26 early and 76 mid-advanced patients. Univariate analysis of variance screened out statistically significant differences among inflammatory markers Cys C and RANTES. The average Cys C level in the mid-advanced stage was significantly higher than in the early stage (p < 0.001) but not for RANTES (p = 0.740). The LASSO logistic regression model (λ.1se = 0.061) associated with UPDRS-I, UPDRS-II, UPDRS-III, HAMA, PDQ-39, and Cys C as the included independent variables revealed that the Model C discrimination and calibration (AUC = 0.968, Brier = 0.049) were superior to Model A (AUC = 0.926, Brier = 0.079) and Model B (AUC = 0.929, Brier = 0.071) models. CONCLUSION: The study results show multiple factors are linked with PD assessment. Moreover, the inflammatory marker Cys C and transcranial sonography measurement could objectively predict PD symptom severity, helping doctors monitor PD evolution in patients while targeting interventions.

ER: a critical hub for STING signaling regulation.

The Stimulator of Interferon Genes (STING) has a crucial role in mediating the immune response against cytosolic double-stranded DNA (dsDNA) and its activation is critically involved in various diseases. STING is synthesized, modified, and resides in the endoplasmic reticulum (ER), and its ER exit is intimately connected with its signaling. The ER, primarily known for its roles in protein folding, lipid synthesis, and calcium storage, has been identified as a pivotal platform for the regulation of a wide range of STING functions. In this review, we discuss the emerging factors that regulate STING in the ER and examine the interplay between STING signaling and ER pathways, highlighting the impacts of such regulations on immune responses and their potential implications in STING-related disorders.

Single-cell analysis of isoform switching and transposable element expression during preimplantation embryonic development.

Alternative splicing is an essential regulatory mechanism for development and pathogenesis. Through alternative splicing one gene can encode multiple isoforms and be translated into proteins with different functions. Therefore, this diversity is an important dimension to understand the molecular mechanism governing embryo development. Isoform expression in preimplantation embryos has been extensively investigated, leading to the discovery of new isoforms. However, the dynamics of isoform switching of different types of transcripts throughout the development remains unexplored. Here, using single-cell direct isoform sequencing in over 100 single blastomeres from the mouse oocyte to blastocyst stage, we quantified isoform expression and found that 3-prime partial transcripts lacking stop codons are highly accumulated in oocytes and zygotes. These transcripts are not transcription by-products and might play a role in maternal to zygote transition (MZT) process. Long-read sequencing also enabled us to determine the expression of transposable elements (TEs) at specific loci. In this way, we identified 3,894 TE loci that exhibited dynamic changes along the preimplantation development, likely regulating the expression of adjacent genes. Our work provides novel insights into the transcriptional regulation of early embryo development.

Acceleration Mechanism of Steel Slag Hydration Using THEED.

In this paper, the strength development of a pure steel slag (SS) system with various concentrations of N,N,N',N'-Tetrakis-(2-hydroxyethyl) ethylenediamine (THEED) was investigated. The hydration kinetics, pore structure and microstructure of SS pastes with and without THEED were characterized to underscore the working mechanism of THEED. Results show that THEED additions significantly increase the 3, 7 and 28 days compressive strength of hardened SS pastes. The enhancement effect increases with the dosage of THEED. At a concentration of 2000 ppm, THEED increased the compressive strength by 733%, 665%, and 545% at 3, 7 and 28 days, respectively. It is confirmed that THEED additions improve the hydration degree of SS by accelerating hydration of the aluminum phase (C3A, PDF-38-1429; C12A7, PDF-48-1882) and C2F,( PDF 38-0408) to generate Mc (PDF-41-0219) and Pa (PDF-30-0222) in the presence of CaCO3. Also, the hydration degree of silicates is increased by THEED. In this way, THEED additions refine the pore structure of hardened SS paste by increasing the pore volume with a diameter below 300 nm to achieve enhancement. The chelating effect of THEED results in promoting dissolution of SS, which provides the driving force for accelerating SS hydration.

1-Pyrroline-5-carboxylate inhibit T cell glycolysis in prostate cancer microenvironment by SHP1/PKM2/LDHB axis.

BACKGROUND: Our previous studies demonstrated that 1-Pyrroline-5-carboxylate (P5C) released by prostate cancer cells inhibits T cell proliferation and function by increasing SHP1 expression. We designed this study to further explore the influence of P5C on T cell metabolism, and produced an antibody for targeting P5C to restore the functions of T cells. METHOD: We co-immunoprecipated SHP1 from T cells and analyzed the proteins that were bound to it using liquid chromatography mass spectrometry (LC/MS-MS). The influence of P5C on T cells metabolism was also detected by LC/MS-MS. Seahorse XF96 analyzer was further used to identify the effect of P5C on T cells glycolysis. We subsequently designed and produced an antibody for targeting P5C by monoclonal technique and verified its effectiveness to restore the function of T cells in vitro and in vivo. RESULT: PKM2 and LDHB bind SHP1 in T cells, and P5C could increase the levels of p-PKM2 while having no effect on the levels of PKM2 and LDHB. We further found that P5C influences T cell energy metabolism and carbohydrate metabolism. P5C also inhibits the activity of PKM2 and decreases the content of intracellular lactic acid while increasing the activity of LDH. Using seahorse XF96 analyzer, we confirmed that P5C remarkably inhibits glycolysis in T cells. We produced an antibody for targeting P5C by monoclonal technique and verified that the antibody could oppose the influence of P5C to restore the process of glycolysis and function in T cells. Meanwhile, the antibody also inhibits the growth of prostate tumors in an animal model. CONCLUSION: Our study revealed that P5C inhibits the process of glycolysis in T cells by targeting SHP1/PKM2/LDHB complexes. Moreover, it is important that the antibody for targeting P5C could restore the function of T cells and inhibit the growth of prostate tumors.

Conserved mechanisms of self-renewal and pluripotency in mouse and human ESCs regulated by simulated microgravity using a 3D clinostat.

Embryonic stem cells (ESCs) exhibit unique attributes of boundless self-renewal and pluripotency, making them invaluable for fundamental investigations and clinical endeavors. Previous examinations of microgravity effects on ESC self-renewal and differentiation have predominantly maintained a descriptive nature, constrained by limited experimental opportunities and techniques. In this investigation, we present compelling evidence derived from murine and human ESCs, demonstrating that simulated microgravity (SMG)-induced stress significantly impacts self-renewal and pluripotency through a previously unidentified conserved mechanism. Specifically, SMG induces the upregulation of heat shock protein genes, subsequently enhancing the expression of core pluripotency factors and activating the Wnt and/or LIF/STAT3 signaling pathways, thereby fostering ESC self-renewal. Notably, heightened Wnt pathway activity, facilitated by Tbx3 upregulation, prompts mesoendodermal differentiation in both murine and human ESCs under SMG conditions. Recognizing potential disparities between terrestrial SMG simulations and authentic microgravity, forthcoming space flight experiments are imperative to validate the impact of reduced gravity on ESC self-renewal and differentiation mechanisms.

Adolescents' relationships with parents and romantic partners in eight countries.

INTRODUCTION: Creating romantic relationships characterized by high-quality, satisfaction, few conflicts, and reasoning strategies to handle conflicts is an important developmental task for adolescents connected to the relational models they receive from their parents. This study examines how parent-adolescent conflicts, attachment, positive parenting, and communication are related to adolescents' romantic relationship quality, satisfaction, conflicts, and management. METHOD: We interviewed 311 adolescents at two time points (females = 52%, ages 15 and 17) in eight countries (China, Colombia, Italy, Kenya, the Philippines, Sweden, Thailand, and the United States). Generalized and linear mixed models were run considering the participants' nesting within countries. RESULTS: Adolescents with negative conflicts with their parents reported low romantic relationship quality and satisfaction and high conflicts with their romantic partners. Adolescents experiencing an anxious attachment to their parents reported low romantic relationship quality, while adolescents with positive parenting showed high romantic relationship satisfaction. However, no association between parent-adolescent relationships and conflict management skills involving reasoning with the partner was found. No associations of parent-adolescent communication with romantic relationship dimensions emerged, nor was there any effect of the country on romantic relationship quality or satisfaction. CONCLUSION: These results stress the relevance of parent-adolescent conflicts and attachment as factors connected to how adolescents experience romantic relationships.